Covalent attachment of a polymer to an enzyme produces a new material, an enzyme-polymer conjugate. The enzymes in such conjugates usually retain catalytic activity but can show modified specifity toward substrates, altered immunogenicity, or changed rates of body clearing. These materials have thus evoked substantial interest for use in enzyme-replacement therapies or other situations where enzymes are administered. Enzyme-polymer conjugates also provide a tractable model for membrane-bound enzyme systems. The nature of the supporting polymer in these conjugates is subject to considerable manipulation by synthetic techniques and may exert substantial effects on the kinetics of the catalyzed reaction; in some cases the polymer appears to bring about structural changes in the active site region of the enzyme. The physicochemical characterizaion of enzyme-polymer conjugates has been largely neglected in spite of the potential for more rational control of desired properties should information about the influence of polymer on the structure of conjugated protein be available. It is the purpose of the work proposed herein (1) to learn more about what happens to the structure of an enzymic active site when the protein is covalently linked to a supporting polymer and (2) to explore the nature of enzyme-polymer interactions in these conjugates. A variety of approaches, involving magnetic resonance experiments, chemical cross-linking and the synthesis of specially tailored polymers, will be used.